3,6,6-Trimethylbicyclo[3.1.0]hexane derivatives as pyrethroid intermediates

ABSTRACT

4-Formyl-3,6,6-trimethylbicyclo[3.1.0]hex-3-ene is oxidized in one vessel by a peroxy acid via 3,4-epoxy-4-formyl-3,6,6-trimethylbicyclo[3.1.0]hexane and 3,4-epoxy-4-formyloxy-3,6,6-trimethylbicyclo[3.1.0]hexane to 3,6,6-trimethyl-3-hydroxybicyclo[3.1.0]hexane-4-one. The four compounds are novel and are intermediates to pyrethroid insecticides.

This is a division of application Ser. No. 189,982, filed Sept. 23,1980, now U.S. Pat. No. 4,284,820, issued Aug. 18, 1981.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to new 3,6,6-trimethylbicyclo[3.1.0]hexanederivatives and to processes for their preparation. These compounds areuseful materials in the preparation of insecticidally active syntheticpyrethroids.

2. Description of the Prior Art

The invention relates to a compound and to a process for itspreparation. This compound is a useful intermediate in the preparationof insecticidally active compounds. The latter compounds are of thepyrethrin type and may, therefore, be called "pyrethroids". As thesepyrethroids combine exceptionally good insecticidal properties with avery low mammalian toxicity, they are of great interest to theagrochemical industry and considerable effort has been expended infinding economic routes for their production.

The general formula of one class of these pyrethroids described in U.S.Pat. No. 4,024,163 may be represented as follows: ##STR1## where eachasterisk denotes an asymmetric carbon atom, each X represents a halogenatom and R is a member of a group of radicals known to impartinsecticidal activity to the molecule, for example, 3-phenoxybenzyl oralpha-cyano-3-phenoxybenzyl. It is known that for maximum insecticidalactivity the acid part of the ester of formula I should be in the(1R,cis) form, i.e. the absolute configuration at carbon atom 1 is R andthe two hydrogen atoms on carbon atoms 1 and 3 are in a cisrelationship. This nomenclature is known as the Elliott nomenclature andis defined in M. Elliott et al., Nature, 248(1974)710.

It follows, therefore, that if these stereoisomeric esters of formula Iare to be prepared, either a stereospecific chemical route is requiredor the desired stereoisomer must be obtained from a racemic form byphysical separation techniques. The latter are expensive and laboriousand are not readily employed on an industrial scale. In astereo-specific route the naturally occurring substance (+)-3-carene isused, whose formula is as follows: ##STR2## This compound is aninexpensive, readily available natural terpene, which is used as astarting material for the preparation of pyrethroid esters of formula I,via a stereospecific route involving processes disclosed in the presentdescription.

SUMMARY OF THE INVENTION

The invention provides the compound3,6,6-trimethyl-3-hydroxybicyclo[3.1.0]hexan-4-one per se. Thiscompound--also referred to hereinafter as "compound D"--has thefollowing structural formula: ##STR3##

The invention also provides a process for the preparation of compound D,characterized in that4-formyl-3,6,6-trimethylbicyclo[3.1.0]hex-3-ene---also referred tohereinafter as "compound A"--is epoxidized with formation of3,4-epoxy-4-formyl-3,6,6-trimethylbicyclo[3.1.0]hexane--also referred tohereinafter as "compound B"--which is oxidized with formation of3,4-epoxy-4-formyloxy-3,6,6-trimethylbicyclo[3.1.0]hexane--also referredto hereinafter as "compound C"--and the latter compound is oxidized.

Compounds A, B and C have the following structural formulae: ##STR4##

Compound A may be prepared as described in Chemical Abstracts71(1969)-123728S. viz. by reacting2,2-dimethyl-3-(2-oxopropyl)cyclopropylethanal with piperidine in thepresence of acetic acid and hydroquinone. The latter aldehyde, in turn,can be prepared as described in British patent application No.7,913,462.

Compounds B and C are also novel and the invention also provides thesetwo compounds per se. Owing to the presence of two chiral carbon atomsin the cyclopropane ring compounds, A, B, C and D exist in two opticalisomers (the presence of the other chiral carbon atoms in the moleculebeing ignored), one having the 1R and the other the 1S configuration.The number 1 indicates the carbon atom of the cyclopropane ring bound tothe group --C--C(H)═O (compounds A and B), --C--O--C(H)═O (compound C)and --C═O (compound D). Compounds B and C may have either the 1R or the1S configuration or they may have a mixture of the two configurations.The 1R configuration of compounds B and C is preferred, because they areprecursors to pyrethoids of formula I having the (1R,cis) configuration.

The epoxidation of compound A can be carried out with any suitableepoxidation agent, for example (a) a peroxy acid or (b) hydrogenperoxide in combination with an epoxidation catalyst, (c) an alkylhydroperoxide, for example, tert-butyl hydroperocide, in combinationwith an epoxidation catalyst or (d) hydrogen peroxide in combinationwith a base, for example sodium carbonate. Peroxy acids are preferred,because they rapidly and quantitatively convert compound A with a highselectivity to compound B.

The selectivity to a certain compound, expressed in a percentage, isdefined as

    (a/b)×100,

wherein "a" is the amount of the starting compound converted into thatcertain compound and "b" is the amount of converted starting compound.

The oxidation of compound B to compound C is a so-called Baever-Villigeroxidation, as described in "Methoden der organischen Chemie"(Houben-Weyl) Book VII/2b (1976) pages 1984-1986, and is suitablycarried out with a peroxy acid, thus giving a high yield of compound C.

The invention also provides a process for the preparation of compound D,characterized in that compound C is oxidized or hydrolyzed. Thisoxidation is also suitably carried out with a peroxy acid and thehydrolysis can be performed in the presence of a base or an acid.

Preferred peroxy acids are an optionally substituted perbenzoic acid(e.g. 3-chloroperbenzoic acid) and peracetic acid. Examples of othersuitable peroxy acids are persulphuric acid, perphthalic acid,persuccinic acid and pernonanoic acid.

The processes provided by the invention are suitably carried out in asolvent, for example, dichloromethane, chloroform, carbon tetrachloride,1,2-dichloroethane, acetone, ethyl acetate, tert-butanol or acetic acid.Very good results have been obtained with chloroform.

According to a preferred embodiment of the present invention theepoxidation of compound A with formation of compound B, the oxidation ofcompound B with formation of compound C and the oxidation of compound Cwith formation of compound D are carried out with the aid of a peroxyacid in a single step. This embodiment has the advantage of requiringonly one agent for the epoxidation and subsequent oxidations, which areall effected in one reaction zone, without isolation of the intermediatecompounds B and C.

The processes provided by the invention are suitably carried out at atemperature in the range of from, for example, 0° C. to 50° C.; anadvantage is that these reactions usually proceed very well at atemperature in the range of from 15° C. to 40° C. Ambient temperature,for example, may be used. The above-described one step process issuitably carried out at a molar ratio of peroxy acid to compound A inthe range of from 3 to 5, but molar ratios higher than 5 are notprecluded.

Compound D can be oxidized with hydrogen peroxide in the presence of analkali metal hydroxide with formation of2,2-dimethyl-3-(2-oxopropyl)cyclopropanecarboxylic acid. This acid maybe converted as described in, for example, British patent applicationNo. 7,912,133 and its corresponding, copending U.S. Ser. No. 135,405,filed Mar. 31, 1980, now U.S. Pat. No. 4,257,956, for example, byforming the corresponding known alkyl ester of this acid and convertingit to the pyrethroid acid (I) using the two-step process described inEuropean Pat. No. 2,849 or using the process described in the earliermentioned U.S. Pat. No. 4,024,163.

The following Examples further illustrate the invention. Conversions andselectivities were determined by nuclear magnetic resonance (NMR)spectroscopy. The absorptions given are relative to a tetramethylsilanestandard and the compounds were dissolved in deuterochloroform.Compounds A, B, C and D all had the 1R configuration. The3-chloroperbenzoic acid contained about 15%w of 3-chlorobenzoic acid,calculated on 3-chloroperbenzoic acid.

EXAMPLES I-V

A round-bottomed flask provided with a stirrer and placed in a waterbath having a temperature between 0° C. and 5° C. was charged with astarting compound and chloroform. Then, 3-chloroperbenzoic acid wasgradually added over a period of one hour. The water bath was taken awayand stirring was continued for 4 hours, while the temperature wasallowed to rise to 20° C. Subsequently, so much dimethyl sulphide wasadded that all of the peroxides present reacted away and stirring wascontinued for 30 minutes. Then, the mixture was filtered, the filtratewas washed twice with a saturated aqueous solution of sodium hydrogencarbonate and twice with a 10%w aqueous solution of sodium chloride, thewashed solution was dried over anhydrous magnesium sulphate and thesolvent was evaporated from the dried solution at a pressure of 2.6 kPato leave an oily residue.

Table I shows which starting compounds were used and the amountsthereof, the volumes of the chloroform and the amounts of3-chloroperbenzoic acid and presents the results of five suchexperiments. An "X" means that the compound could not be detected.

    __________________________________________________________________________    Starting                                                                      compound           3-chloroperben-   Selectivity, %,                                  amount,                                                                            Chloroform                                                                          zoic acid                                                                             Conversion of start-                                                                    to compound                              Example                                                                            name                                                                             mmol ml    mmol    ing compound, %                                                                         B C D                                    __________________________________________________________________________     I   A  0.80  5    0.96     70       30                                                                              70                                                                              X                                     II  A  20   40    40      100       10                                                                              80                                                                              10                                    III A  0.80  5    2.9     100       X X above 90                              IV  A  23.3 70    93.2    100       X X above 90.sup.(1)                      V   C  13.9 25    20.9     95       X X above 90.sup.(2)                     __________________________________________________________________________     .sup.(1) isolated yield 85%                                                   .sup.(2) isolated yield 90%                                              

The NMR spectra showed the following absorptions:

Compound B

The proton NMR data are as follows:

    ______________________________________                                        multiplets for CH.sub.2 --CH--CH                                              ______________________________________                                        δ = 1.01 ppm, singlet,                                                                     δ = 1.09 ppm, singlet,                               CH.sub.3 --C--CH.sub.3                                                                           CH.sub.3 --C--CH.sub.3                                     δ = 1.47 ppm, singlet,                                                                     δ = 9.40 ppm, singlet,                               CH.sub.3 --C--O--  CH═O                                                   ______________________________________                                    

Compound C

The proton NMR data are as follows:

    ______________________________________                                        multiplets for CH.sub.2 --CH--CH                                              ______________________________________                                        δ = 1.05 ppm, singlet,                                                                     δ = 1.11 ppm, singlet,                               CH.sub.3 --C--CH.sub.3                                                                           CH.sub.3 --C--CH.sub.3                                     δ = 1.37 ppm, singlet,                                                                     δ = 8.27 ppm, singlet,                               CH.sub.3 --C--O--  CH═O                                                   ______________________________________                                    

The ¹³ C NMR data are as follows:

    ______________________________________                                                    δ (ppm)     J (Hz)                                          ______________________________________                                        CH.sub.3 --C--CH.sub.3                                                                      15.4        quartet 129                                         CH.sub.3 --C--CH.sub.3                                                                      26.2        quartet 126                                         CH.sub.3 --C--CH.sub.3                                                                      30.6        singlet --                                          CH.sub.2 --CH 24.1        doublet 170                                         HC--C(--O)--O--                                                                             33.9        doublet 170                                         CH.sub.2 --CH 31.6        triplet 129                                         CH.sub.2 --C--O                                                                             65.5        singlet --                                          CH.sub.3 --C--O                                                                             14.5        quartet 129                                         HC--C(--O)--O--                                                                             80.3        singlet --                                          O--CH         159.6       doublet 230                                         ______________________________________                                    

Compound D

The proton NMR data are as follows:

δ=1.04 ppm, 1.17 ppm and 1.24 ppm, three singlets for CH₃ --C--CH₃ andCH₃ --C--OH

δ=1.98 ppm, doublet, H--C--C═O;J=5 Hz

δ=2.2 ppm, doublet of doublet, HC--CH(H); J₁ =15 Hz, J₂ =6 Hz

δ=1.84 ppm, doublet, HC--CH(H); J=15 Hz

δ=1.98 ppm, doublet of doublet, HC--CH₂ ; J₁ =5 Hz, J₂ =6 Hz variable,broad singlet, --OH.

The ¹³ C NMR data are as follows:

    ______________________________________                                                  δ (ppm)      J (Hz)                                           ______________________________________                                        CH.sub.3 --C--CH.sub.3                                                                    17.0         quartet 125.6                                        CH.sub.3 --C--CH.sub.3                                                                    27.3         quartet 125.6                                        CH.sub.3 --C--CH.sub.3                                                                    29.3         singlet --                                           CH.sub.2 --CH                                                                             31.6         doublet 171.4                                        HC--C═O 39.3         doublet 173.1                                        CH.sub.2 --CH                                                                             35.0         triplet 130.7                                        C--OH       80.2         singlet --                                           CH.sub.3 --C--OH                                                                          20.5         quartet 125.6                                        C═O     20.8         singlet --                                           ______________________________________                                    

I claim:
 1. 3,4-Epoxy-4-formyloxy-3,6,6-trimethylbicyclo[3.1.0]hexane,having the 1R configuration in which 1 denotes the carbon atom of thecyclopropane ring bonded to the group --C--O--C(H)═O.